ABSTRACT Infection with HIV significantly increases the risk of developing cancer. In the era of widespread availability of antiretroviral therapy, the incidence of some cancers has declined but overall the number of new cases has grown annually. Cancer has become a leading cause of death in people living with HIV. Despite more than three decades of research on HIV and cancer, substantial gaps remain in understanding how HIV-infection potentiates the development of cancers and why cancer is more aggressive among persons with HIV infection. New strategies are needed for the prevention and treatment of HIV-associated malignancies (HIVAM), and developing these approaches will require careful translational, clinical and epidemiologic investigations. The UW/Fred Hutch CFAR HIVAM Core began as a Scientific Working Group in 2010; after building a large community of researchers in this field in Seattle, it developed into a Core for the 2013-2018 funding cycle. The HIVAM Core has helped to catalyze, support and sustain impactful research on cancer in the context of HIV infection. Core membership has grown to nearly 50 faculty and scientific staff. New collaborations facilitated by the Core have led to 2 NIH- sponsored program project grants, several R01s, one R21, multiple K23s, and 3 training grants. Assays and data services provided by the Core have helped to facilitate these activities. Looking ahead to the next five-year cycle, the HIVAM Core will meet the needs of a growing research community by offering the latest technology to study cancer in the context of HIV infection and availing researchers to a suite of data instrument tools and access to unique clinical cohorts and biospecimens through three Specific Aims. Specific Aim 1 seeks to enhance the quality and quantity of data collected about the incidence, etiology, natural history and sequelae of cancer arising among persons with HIV infection to inform studies in both cancer prevention and treatment. To achieve this objective, the Core will identify large cohorts of HIV-infected persons to specifically design cancer endpoints or analyses into planned, ongoing and completed studies. These include studies conducted by the HVTN, HPTN, MTN, AMC, ACTG and others, many of which are fully- or partially-based in Seattle and have UW/FH CFAR investigator representation. Specific Aim 2 seeks to facilitate the collection and distribution of biospecimens suitable for translational studies focused on the biology of HIVAM. The HIVAM Core will preserve and expand an existing repository for HIVAM with nearly 200,000 biospecimens and make these available to the scientific community. This work notably leverages existing repositories from affiliated investigators and cohorts, rather than requiring maintenance or creation of a new biorepository. In Specific Aim 3, novel laboratory assays for the study of HIVAM will be developed and disseminated. These will include assays for detection and quantification of tumor viruses (i.e., low-cost HPV detection and genotyping), genomic analyses of HIV-associated tumors, and assays to evaluate the role of inflammation in the genesis and progression of HIVAM. Taken together, the HIVAM Core is well-poised to support catalytic research in cancers within the context of HIV.